MARCKS and Lung Disease

Sheats, M. Katie; Yin, Qi; Fang, Shiaofen; Park, Joungjoa; Crews, Anne L.; Parikh, Indu; Dickson, Brian; Adler, Kenneth B.

doi:10.1165/rcmb.2018-0285tr

Cited by 23 publications

(11 citation statements)

References 161 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon activation by PKC signaling, MARCKS translocates from the plasma membrane to the cytoplasm and regulates many cellular processes depending on actin remodeling, such as membrane trafficking and phagocytosis. MARCKS has been shown to be involved in lung diseases, including COPD and asthma 82 , probably because of its ability to regulate mucin secretion and inflammation 83 . Activation of PKC, either directly or through secreted cytokines, is generally viewed a common event during viral infections, including human immunodeficiency virus in promonocytic cells, respiratory syncytial virus in bronchial epithelial cells 84 , 85 , and hepatitis B virus transactivator HBx 86 .…”

Section: Discussionmentioning

confidence: 99%

Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells

George

Revikumar

Paul

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Although a defective vitamin D endocrine system has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D endocrine system and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D endocrine system in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes, as potentially modulated by vitamin D endocrine system, were identified in transcriptomic datasets from patient’s cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D endocrine system in SARS-CoV-2-infected cells. Protein–protein interaction network of differentially expressed vitamin D-modulated genes were enriched in the immune system, NF-κB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results presented here povide computational evidence to implicate a dysregulated vitamin D endocrine system in the pathobiology of SARS-CoV-2 infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells

George

Revikumar

Paul

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These findings suggest that the interaction between undifferentiated CD44 hi MPCs and hyaluronic acid in the fibroblastic focus may serve to drive progression of fibrosis in IPF. MARCKS is a target of protein kinase C that serves to catalyze actin filament crosslinking to promote cell motility and mitogenesis 45 . MARCKS has been linked to metastasis in multiple cancers 46 , and plays a role in maintaining the cancer associated fibroblast phenotype 47 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals that lung mesenchymal progenitor cells in IPF exhibit pathological features early in their differentiation trajectory

Beisang

Smith

Yang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

In Idiopathic Pulmonary Fibrosis (IPF), there is unrelenting scarring of the lung mediated by pathological mesenchymal progenitor cells (MPCs) that manifest autonomous fibrogenicity in xenograft models. To determine where along their differentiation trajectory IPF MPCs acquire fibrogenic properties, we analyzed the transcriptome of 335 MPCs isolated from the lungs of 3 control and 3 IPF patients at the single-cell level. Using transcriptional entropy as a metric for differentiated state, we found that the least differentiated IPF MPCs displayed the largest differences in their transcriptional profile compared to control MPCs. To validate entropy as a surrogate for differentiated state functionally, we identified increased CD44 as a characteristic of the most entropic IPF MPCs. Using FACS to stratify IPF MPCs based on CD44 expression, we determined that CD44hi IPF MPCs manifested an increased capacity for anchorage-independent colony formation compared to CD44lo IPF MPCs. To validate our analysis morphologically, we used two differentially expressed genes distinguishing IPF MPCs from control (CD44, cell surface; and MARCKS, intracellular). In IPF lung tissue, pathological MPCs resided in the highly cellular perimeter region of the fibroblastic focus. Our data support the concept that IPF fibroblasts acquire a cell-autonomous pathological phenotype early in their differentiation trajectory.

show abstract

“…Increased intracellular Ca 2+ concentration activates PKC, which phosphorylates MARCKS and thereby induces its translocation from the PM to the cytosol. MARCKS translocation from the PM can decrease actin filament crosslinking in the cell cortex and increase PIP 2 availability, which facilitates cortical actin dynamics during exocytosis [62].…”

Section: Dockingmentioning

confidence: 99%

Actin and Myosin in Non-Neuronal Exocytosis

Miklavc

Frick

2020

Cells

View full text Add to dashboard Cite

Cellular secretion depends on exocytosis of secretory vesicles and discharge of vesicle contents. Actin and myosin are essential for pre-fusion and post-fusion stages of exocytosis. Secretory vesicles depend on actin for transport to and attachment at the cell cortex during the pre-fusion phase. Actin coats on fused vesicles contribute to stabilization of large vesicles, active vesicle contraction and/or retrieval of excess membrane during the post-fusion phase. Myosin molecular motors complement the role of actin. Myosin V is required for vesicle trafficking and attachment to cortical actin. Myosin I and II members engage in local remodeling of cortical actin to allow vesicles to get access to the plasma membrane for membrane fusion. Myosins stabilize open fusion pores and contribute to anchoring and contraction of actin coats to facilitate vesicle content release. Actin and myosin function in secretion is regulated by a plethora of interacting regulatory lipids and proteins. Some of these processes have been first described in non-neuronal cells and reflect adaptations to exocytosis of large secretory vesicles and/or secretion of bulky vesicle cargoes. Here we collate the current knowledge and highlight the role of actomyosin during distinct phases of exocytosis in an attempt to identify unifying molecular mechanisms in non-neuronal secretory cells.

show abstract

MARCKS and Lung Disease

Cited by 23 publications

References 161 publications

Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells

Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells

Single-cell RNA sequencing reveals that lung mesenchymal progenitor cells in IPF exhibit pathological features early in their differentiation trajectory

Actin and Myosin in Non-Neuronal Exocytosis

Contact Info

Product

Resources

About